PXD007851 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A Chemproteomics Approach to Query the Degradable Kinome Using a Multi-kinase Degrader |
Description | Heterobifunctional molecule that recruits E3 ubiquitin ligases, such as cereblon, for targeted protein degradation is an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK and 9 members of the CDK family, as degradable. This set of kinases is only a fraction of the intracellular targets bound by the degrader, demonstrating that successful degradation requires more than target engagement. The results guided us to develop selective degraders for FLT3 and BTK, with potentials to improve disease treatment. Together, this study demonstrates an efficient approach to triage a gene family of interest to identify readily degradable targets for further studies and pre-clinical developments. |
HostingRepository | PRIDE |
AnnounceDate | 2017-11-08 |
AnnouncementXML | Submission_2018-05-23_06:17:32.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Eric Fischer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-09-27 02:35:42 | ID requested | |
1 | 2017-11-08 00:04:17 | announced | |
⏵ 2 | 2018-05-23 06:17:34 | announced | Updated publication reference for PubMed record(s): 29129717. |
Publication List
Huang HT, Dobrovolsky D, Paulk J, Yang G, Weisberg EL, Doctor ZM, Buckley DL, Cho JH, Ko E, Jang J, Shi K, Choi HG, Griffin JD, Li Y, Treon SP, Fischer ES, Bradner JE, Tan L, Gray NS, A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader. Cell Chem Biol, 25(1):88-99.e6(2018) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: kinase |
Contact List
Eric S. Fischer |
contact affiliation | BCMP, Harvard Medical School, Boston, USA Cancer Biology, Dana-Farber Cancer Institute, Boston, USA |
contact email | eric_fischer@dfci.harvard.edu |
lab head | |
Eric Fischer |
contact affiliation | Dana-Farber Cancer Institute |
contact email | eric_fischer@dfci.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/11/PXD007851 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD007851
- Label: PRIDE project
- Name: A Chemproteomics Approach to Query the Degradable Kinome Using a Multi-kinase Degrader